Alkaline phosphatase isoenzymes can appropriately be regarded as tissue-specific antigens, in that the alkaline phosphatases of different organs have been distinguished from one another immunochemically. The isoenzyme found in the human placentae has been found to be distinct in its biochemical and immunochemical properties from any isoenzyme found in normal adult tissues. In 1968, it was learned that some cancer patients produced an isoenzyme which closely resembled the placental isoenzyme, the "Regan isoenzyme." If this is a product of the same gene as placental phosphatase then its expression in cancer can appropriately be regarded as derepression of the synthesis of this enzyme. There is serious doubt that these enzymes are products of the same gene, however, since variant isoenzymes have been described in cancer patients which can be distinguished from the placental isoenzyme. It is proposed that the cancer patient enzymes be compared structurally with the placental isoenzyme. This would determine whether the observed diferences in biochemical properties are related to distinct structural components of the variant enzymes. If a difference in structure between the cancer patient and placental enzyme is consistently observed this would strongly indicate that they are distinct proteins, and would suggest that it is not the placental enzyme which is appearing in cancer. Immunochemical techniques would be used to attempt to identify antigenic determinants which are unique to the variant enzymes. The production of antisera in chickens, rabbits and monkeys should yield reagents which recognize different antigenic determinants. Comparison of immunochemical cross-reactivity will be by double diffussion, electrophoretic retardation, complement fixation, radial immunodiffusion and immunoabsorption. Antisera which can discriminate one specific variant could be used to identify and isolate peptides specific for that variant, and to determine whether a given adult tissue contains trace amounts of enzyme.